Infection with HIV and Acquired Immune Deficiency Syndrome (AIDS) continues to increase worldwide, despite intense research to control its spread. Furthermore, the emergence of new viral infections presents additional challenges to public health.
Therapies to treat infection that target viruses may be limited in efficacy due to resistance and genetic variance of the virus.
HIV infection is mediated by the viral fusion glycoprotein gp120-gp41 binding the cell surface expressed receptor CD4. This binding is the basis of the viral targeting of T lymphocytes and monocyte macrophages. The receptor gp120 shows an affinity in vitro for several glycosphingolipids (GSLs) (Bhat at al (1993); Fantini at al (1998); Mylvaganam and Lingwood (1999a)).
A need exists for glycolipid mimics that are dispersible in biocompatible media and can be used to modify the interaction between naturally occurring membrane incorporated glycoconjugates, such as GSLs, and the receptors expressed by a virus. Such water soluble glycolipid mimics have been recognized as having potential for use in the preventative treatment of individuals at risk of infection from viruses such as HIV.
Lund et al (2006) have investigated the effect of the water soluble glycolipid mimic adamantylGb3 on HIV infection of cells in culture. In previous studies adamantylGb3 had been demonstrated to be a superior ligand for the receptor gp120 (Mahfoud at al (2002)).
A dose dependent inhibition of infection of Jurkat T cells by HIV-1 pre-incubated with adamantylGb3 has been demonstrated in vitro (Lund et al 2006). The in vivo inhibition of infection by HIV-1 was not reported, but the water soluble glycolipid mimic was indicated to have no effect on Jurkat T cell viability. Transient changes in CD4 surface expression were observed. Lund et al (2006) attributed the dose dependent inhibition of infection to an inhibition of attachment of the pre-treated HIV-1 to the Jurkat T cells. The adamantylGb3 treated virus remained non-host cell attached and virions could not be found within the Jurkat cells.
Further studies on HIV-1 infection of primary lymphoid cells in vitro provided results consistent with those observed for Jurkat T cells as host cells. Infection by both wild type and drug resistant HIV-1 infection was inhibited by the pre-treatment of the water soluble glycolipid mimic adamantylGb3. However, pre-incubation of cells with adamantylGb3 was ineffective.
Lund et al (2006) noted the effective concentration range required to inhibit HIV-1 infection would be difficult to maintain clinically, but suggested the formulation of adamantylGb3 within a cream might provide a topical ointment for the prevention of mucosal HIV infection.
It is an object of the invention to provide receptor binding carbohydrate-lipid constructs that are effective to inhibit viral infection of the cells of a subject.
It is a further object of the invention to provide receptor binding carbohydrate-lipid constructs that are effective to promote clearance of virus from an infected subject.
These objects are to be read disjunctively with the object of to at least provide a useful choice.